Contact Information

Research Interests

The mechanism of action of small molecules and the fundamental biological role of protein tyrosine phosphatases

Research Description

The primary research focus of the Lazo Laboratory is on the mechanism of action and of resistance to novel and existing anticancer agents, particularly natural products, and on the fundamental biological role of protein tyrosine phosphatases.

We are currently studying small molecules that disrupt the interactions of the oncoprotein c-Myc with its partner Max to determine their usefulness as anticancer agents. We have developed a human tumor stem cell model that permits the interrogation of chemical libraries and small interference RNA libraries to identify compounds and pathways that control the survival of tumor stem cells. Similarly, we are studying small molecules and intracellular pathways that mitigate or enhance the toxic effects of radiation. Some of the high throughput approaches we use are broadly applicable to other pathological conditions including neurodegenerative diseases, such as Alzheimer's, and neglected diseases, such as leishmaniasis.

A second major research project focuses on investigating how protein tyrosine phosphatases, such as mitogen-activated protein kinase phosphatases, Cdc25, and phosphatase of regenerating liver, control cell proliferation, migration, invasion, and survival using both molecular biological and pharmacological approaches and on applying chemical biological methodologies to the discovery of new chemical probes and potential therapeutics. We currently have developed the first phosphatase of regenerating liver knock out mouse model to investigate the role of this unique protein in tumorigenesis. We have discovered several potent and specific small molecule inhibitors of these protein phosphatases and are investigating their pharmacological properties.

Selected Publications

Because novel approaches to drug development require a new and comprehensive understanding of cellular organization and communication, the mechanisms by which cells transmit signals within and among cells is an area of emphasis within the Department. The Department of Pharmacology at the University of Virginia has a distinguished scientific history in the study of cellular signaling processes (signal transduction); two recent Nobel Laureates honored for their work deciphering pathways of cellular signaling conducted this work in the Pharmacology Department at the University of Virginia. Today, faculty of the Department of Pharmacology bring to bear a wide range of scientific approaches and technical methods to address fundamental questions of cellular signaling related to neural transmission, hormone and growth factor signaling, cell cycle regulation, neoplasia and regulation of gene expression.